Development and Validation of an LC–MS/MS Method for the Determination of 2‐Chloro‐1,3‐Bis(dimethylamino)Trimethinium Hexafluorophosphate and Alkyl <i>p</i> ‐Toluenesulfonates in Etoricoxib Drug Substance

ABSTRACT A rapid, sensitive, and selective LC–MS/MS method using multiple reaction monitoring (MRM) acquisition mode was developed and validated for the simultaneous determination of 2‐chloro‐1,3‐bis(dimethylamino)trimethinium hexafluorophosphate (HFP), methyl para‐toluenesulfonate (MPTS), ethyl para‐toluenesulfonate (EPTS), isopropyl para‐toluenesulfonate (IPTS) impurities in etoricoxib active pharmaceutical ingredient (API). The method was established through systematic mass‐based identification and chromatographic optimization, followed by full validation in accordance with ICH guidelines. Chromatographic separation was achieved on an ACE phenyl column using an ammonium acetate buffer and acidified methanol under gradient conditions, with MRM detection in positive ESI mode. The method was linear (correlation coefficients [ r ] ≥ 0.99), precise (%RSD &lt; 6%), accurate (recoveries 78.7%–110.9%), and robust, with low ppm limits of detection and quantification. The method is suitable for routine quality control and regulatory applications.